Thrombotic occlusion remains the most serious complication associated with clinical small caliber grafts used in peripheral vascular surgery and aortocoronary bypass. Although it has been recognized that factors contributing to thrombus formation include both graft and hemodynamic variables, their relative importance has not been defined. Using a baboon arteriovenous shunt model and selected clinical grafts, we propose to measure quantitatively relative rates destruction, and deposition of labeled platelets and fibrinogen, and to assess the effectiveness of various antithrombotic strategies. Initially we will use gamma camera imaging to measure the deposition of 111-In-labeled platelets and 131I-fibrinogen onto expanded Teflon (Gore-Tex) vascular grafts (3-5 mm i.d.). Since this ex vivo system permits repeated studies in a single animal and a high degree of spatial resolution for thrombus detection, localized thrombus deposition within vascular grafts will be systematically measured at various flow rates with respect to the following variables: graft type, length, diameter, degree of stenosis, angle of bifurcation, and radius of curvature. Grafts will also be studied after surface modification by glow discharge polymerization. Acute and chronic alterations in the circulating platelet pool will be assessed by measurements of platelet ADP, ATP, TxB2, PF-4, Beta-TG, and serotonin, and by platelet survival using 14C-serotonin and 111-In. Subsequently, these hypotheses will be tested: (1) that anastomatic intimal hyperplasia is related to the extent of graft-platelet interactions, (2) that graft patency can be restored using tissue-type plasminogen activator, and (3) that the efficacy of conventional antithrombotic therapy (heparin, aspirin, dipyridamole) depends significantly on graft type, geometry, and hemorheologic parameters. The studies are therefore intended to define the operational limits of small caliber grafts, and to permit the selection of optimal therapeutic strategies.